Store-operated Ca²⁺ entry controls ameloblast cell function and enamel development.

Area of Science:

• Cell Biology
• Developmental Biology
• Biochemistry

Background:

• Loss-of-function mutations in STIM1 cause CRAC channelopathy, characterized by dental enamel defects.
• The precise mechanisms underlying these enamel defects remain unclear due to a lack of suitable animal models.

Purpose of the Study:

• To investigate the role of STIM1 and STIM2 in enamel formation using a novel mouse model.
• To elucidate the cellular and molecular mechanisms by which store-operated Ca2+ entry (SOCE) influences ameloblast function and enamel mineralization.

Main Methods:

• Generation of Stim1/2 conditional knockout mice lacking STIM1 and STIM2 in enamel cells.
• Assessment of SOCE, enamel mineralization, ameloblast morphology, and gene expression.
• Analysis of oxidative stress markers and mitochondrial function.

Main Results:

• Stim1/2 deletion in enamel cells impaired SOCE, leading to hypomineralized, mechanically weak, and thin enamel.
• SOCE deficiency altered ameloblast morphology, caused mitochondrial mislocalization, and dysregulated ER stress and glutathione pathways.
• Increased oxidative stress, reduced mitochondrial function, and abnormal mitochondrial morphology were observed in SOCE-deficient ameloblasts.

Conclusions:

• SOCE is essential for maintaining ameloblast function and proper dental enamel mineralization.
• Disruption of SOCE leads to cellular dysfunction, including ER stress and oxidative stress, impacting enamel quality.
• This study provides critical insights into the pathogenesis of CRAC channelopathy-associated enamel defects.